The objective of the proposed study is to develop a histochemical method for the demonstration of cyclic nucleotide phosphodiesterase in the retina. The method is based on lead precipitation of inorganic phosphate liberated from cyclic nucleotides by enzyme action and observation of the electron-opaque lead precipirate by electron microscopy. The histochemical technique will be applied to localize enzyme activity in normal mammalian retina and to evaluate a reported deficiency of phophodiesterase activity in the photoreceptor cells of mice with hereditary retinal degeneration. Further studies are proposed to evaluate the effect of some pharmacological and natural regulators of phosphodiesterase activity, such as papaverine and catecholamines. Finally the histochemical procedure will be applied to primate retina to determine whether there are differences in distribution or activity of enzyme in retinal rods and cones. BIBLIOGRAPHIC REFERENCES: Robb, R.M.: Histochemical evidence of cyclic nucleotide phosphodiesterase in photoreceptor outer segments. Invest. Ophthal. 13:740-747, 1974. Robb, R.M.: Electron microscopic histochemical studies of cyclic 3', 5' -nucleotide phosphodiesterase in the developing retina of normal mice and mice with hereditary retinal degeneration. Tr. Am. Ophthal. Soc. 72: 650-669, 1974.